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330 results on '"Saal, Lao H."'

3. Lung adenocarcinoma promotion by air pollutants

Author

Hill, William, Lim, Emilia L., Weeden, Clare E., Lee, Claudia, Augustine, Marcellus, Chen, Kezhong, Kuan, Feng-Che, Marongiu, Fabio, Evans, Jr, Edward J., Moore, David A., Rodrigues, Felipe S., Pich, Oriol, Bakker, Bjorn, Cha, Hongui, Myers, Renelle, van Maldegem, Febe, Boumelha, Jesse, Veeriah, Selvaraju, Rowan, Andrew, Naceur-Lombardelli, Cristina, Karasaki, Takahiro, Sivakumar, Monica, De, Swapnanil, Caswell, Deborah R., Nagano, Ai, Black, James R. M., Martínez-Ruiz, Carlos, Ryu, Min Hyung, Huff, Ryan D., Li, Shijia, Favé, Marie-Julie, Magness, Alastair, Suárez-Bonnet, Alejandro, Priestnall, Simon L., Lüchtenborg, Margreet, Lavelle, Katrina, Pethick, Joanna, Hardy, Steven, McRonald, Fiona E., Lin, Meng-Hung, Troccoli, Clara I., Ghosh, Moumita, Miller, York E., Merrick, Daniel T., Keith, Robert L., Al Bakir, Maise, Bailey, Chris, Hill, Mark S., Saal, Lao H., Chen, Yilun, George, Anthony M., Abbosh, Christopher, Kanu, Nnennaya, Lee, Se-Hoon, McGranahan, Nicholas, Berg, Christine D., Sasieni, Peter, Houlston, Richard, Turnbull, Clare, Lam, Stephen, Awadalla, Philip, Grönroos, Eva, Downward, Julian, Jacks, Tyler, Carlsten, Christopher, Malanchi, Ilaria, Hackshaw, Allan, Litchfield, Kevin, DeGregori, James, Jamal-Hanjani, Mariam, and Swanton, Charles

Published
2023
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5. Tumor-informed ctDNA as an objective marker for postoperative residual disease in epithelial ovarian cancer.

Author

Paspalj, Valentina, primary, Grimm, Christoph, additional, Postl, Magdalena, additional, Tauber, Christina Viktoria, additional, Segui, Nuria, additional, Brueffer, Christian, additional, Alcaide, Miguel, additional, Oton, Lucia, additional, Chen, Yilun, additional, Saal, Lao H., additional, Hofstetter, Gerda, additional, Muellauer, Leonhard, additional, Kessler, Mirjana, additional, and Trillsch, Fabian, additional

Published
2024
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6. Monitoring ctDNA dynamics in early breast cancer using a novel ultra-sensitive tumor-informed structural variant approach combining whole-genome sequencing and multiplex dPCR.

Author

Saal, Lao H., primary, Loman, Niklas, additional, Chen, Yilun, additional, Alcaide, Miguel, additional, Brueffer, Christian, additional, Gladchuk, Sergii, additional, Dalal, Hina, additional, Meng, Pei, additional, George, Anthony M, additional, Birkeälv, Sofia, additional, Saghir, Hani, additional, Kimbung, Siker, additional, Förnvik, Daniel, additional, Zander, Lina, additional, Honeth, Gabriella, additional, Howarth, Karen, additional, Borg, Åke, additional, Ehinger, Anna, additional, Malmberg, Martin, additional, and Rydén, Lisa, additional

Published
2024
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7. RNA sequencing-based single sample predictors of molecular subtype and risk of recurrence for clinical assessment of early-stage breast cancer

Author

Staaf, Johan, Häkkinen, Jari, Hegardt, Cecilia, Saal, Lao H., Kimbung, Siker, Hedenfalk, Ingrid, Lien, Tonje, Sørlie, Therese, Naume, Bjørn, Russnes, Hege, Marcone, Rachel, Ayyanan, Ayyakkannu, Brisken, Cathrin, Malterling, Rebecka R., Asking, Bengt, Olofsson, Helena, Lindman, Henrik, Bendahl, Pär-Ola, Ehinger, Anna, Larsson, Christer, Loman, Niklas, Rydén, Lisa, Malmberg, Martin, Borg, Åke, and Vallon-Christersson, Johan

Published
2022
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10. Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling.

Author

De Marchi, Tommaso, Lai, Chun-Fui, Simmons, Georgia M., Goldsbrough, Isabella, Harrod, Alison, Lam, Thai, Buluwela, Lakjaya, Kjellström, Sven, Brueffer, Christian, Saal, Lao H., Malmström, Johan, Ali, Simak, and Niméus, Emma

Subjects
ESTROGEN receptors, METASTATIC breast cancer, PROTEOMICS, CYCLIN-dependent kinases, PROTEIN expression, CELLULAR signal transduction, AROMATASE inhibitors, HORMONE therapy
Abstract

Three quarters of all breast cancers express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancer, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and without direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and mTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells. Our study is the first proteome-centric characterization of ESR1 mutant models, out of which we confirm estrogen independence of ER mutants and reveal the enrichment of immune signaling pathways at the proteomic level. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Agreement between molecular subtyping and surrogate subtype classification: a contemporary population-based study of ER-positive/HER2-negative primary breast cancer

Author

Lundgren, Christine, Bendahl, Pär-Ola, Borg, Åke, Ehinger, Anna, Hegardt, Cecilia, Larsson, Christer, Loman, Niklas, Malmberg, Martin, Olofsson, Helena, Saal, Lao H., Sjöblom, Tobias, Lindman, Henrik, Klintman, Marie, Häkkinen, Jari, Vallon-Christersson, Johan, Fernö, Mårten, Rydén, Lisa, and Ekholm, Maria

Published
2019
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12. Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study

Author

Staaf, Johan, Glodzik, Dominik, Bosch, Ana, Vallon-Christersson, Johan, Reuterswärd, Christel, Häkkinen, Jari, Degasperi, Andrea, Amarante, Tauanne Dias, Saal, Lao H., Hegardt, Cecilia, Stobart, Hilary, Ehinger, Anna, Larsson, Christer, Rydén, Lisa, Loman, Niklas, Malmberg, Martin, Kvist, Anders, Ehrencrona, Hans, Davies, Helen R., Borg, Åke, and Nik-Zainal, Serena

Published
2019
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14. Comprehensive molecular comparison of BRCA1 hypermethylated and BRCA1 mutated triple negative breast cancers

Author

Glodzik, Dominik, Bosch, Ana, Hartman, Johan, Aine, Mattias, Vallon-Christersson, Johan, Reuterswärd, Christel, Karlsson, Anna, Mitra, Shamik, Niméus, Emma, Holm, Karolina, Häkkinen, Jari, Hegardt, Cecilia, Saal, Lao H., Larsson, Christer, Malmberg, Martin, Rydén, Lisa, Ehinger, Anna, Loman, Niklas, Kvist, Anders, Ehrencrona, Hans, Nik-Zainal, Serena, Borg, Åke, and Staaf, Johan

Published
2020
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18. Preoperative ctDNA Levels Are Associated With Poor Overall Survival in Patients With Ovarian Cancer.

Author

DOBILAS, ARTURAS, YILUN CHEN, BRUEFFER, CHRISTIAN, LEANDERSSON, PIA, SAAL, LAO H., and BORGFELDT, CHRISTER

Abstract

Background/Aim: Circulating tumor DNA (ctDNA), which is shed from cancer cells into the bloodstream, offers a potential minimally invasive approach for cancer diagnosis and monitoring. This research aimed to assess the preoperative ctDNA levels in ovarian tumors patients' plasma and establish correlations with clinicopathological parameters and patient prognosis. Patients and Methods: Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/ml and variant allele frequency. Results: Somatic mutations were found in 24 tumor samples, 17 of which were from ovarian cancer patients. The most frequently mutated gene was TP53. Preoperative plasma ctDNA levels were detected in 14 of the 24 patients. With higher stage, plasma ctDNA mutant concentration increased (p for trend <0.001). The overall survival of cancer patients with more than 10 ctDNA mutant copies/ml in plasma was significantly worse (p=0.008). Conclusion: Pre-operative ctDNA measurement in ovarian cancer patients' plasma holds promise as a predictive biomarker for tumor staging and prognosis. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling

Author

Roswall, Pernilla, Bocci, Matteo, Bartoschek, Michael, Li, Hong, Kristiansen, Glen, Jansson, Sara, Lehn, Sophie, Sjölund, Jonas, Reid, Steven, Larsson, Christer, Eriksson, Pontus, Anderberg, Charlotte, Cortez, Eliane, Saal, Lao H, Orsmark-Pietras, Christina, Cordero, Eugenia, Haller, Bengt Kristian, Häkkinen, Jari, Burvenich, Ingrid J G, Lim, Elgene, Orimo, Akira, Höglund, Mattias, Rydén, Lisa, Moch, Holger, Scott, Andrew M, Eriksson, Ulf, and Pietras, Kristian

Subjects
Cellular signal transduction -- Genetic aspects -- Health aspects, Breast cancer -- Genetic aspects -- Development and progression -- Care and treatment, Platelet-derived growth factor -- Health aspects, Biological sciences, Health
Abstract

Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable., Author(s): Pernilla Roswall [1, 2]; Matteo Bocci [1]; Michael Bartoschek [1]; Hong Li [2]; Glen Kristiansen [3]; Sara Jansson [4]; Sophie Lehn [1]; Jonas Sjölund [1]; Steven Reid [1]; Christer [...]

Published
2018
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23. Supplementary Spreadsheet S5 from p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes

Author

Pappas, Kyrie, primary, Xu, Jia, primary, Zairis, Sakellarios, primary, Resnick-Silverman, Lois, primary, Abate, Francesco, primary, Steinbach, Nicole, primary, Ozturk, Sait, primary, Saal, Lao H., primary, Su, Tao, primary, Cheung, Pamela, primary, Schmidt, Hank, primary, Aaronson, Stuart, primary, Hibshoosh, Hanina, primary, Manfredi, James, primary, Rabadan, Raul, primary, and Parsons, Ramon, primary

Published
2023
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24. Supplementary Data for Article from p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes

Author

Pappas, Kyrie, primary, Xu, Jia, primary, Zairis, Sakellarios, primary, Resnick-Silverman, Lois, primary, Abate, Francesco, primary, Steinbach, Nicole, primary, Ozturk, Sait, primary, Saal, Lao H., primary, Su, Tao, primary, Cheung, Pamela, primary, Schmidt, Hank, primary, Aaronson, Stuart, primary, Hibshoosh, Hanina, primary, Manfredi, James, primary, Rabadan, Raul, primary, and Parsons, Ramon, primary

Published
2023
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25. Data from p53 Maintains Baseline Expression of Multiple Tumor Suppressor Genes

Author

Pappas, Kyrie, primary, Xu, Jia, primary, Zairis, Sakellarios, primary, Resnick-Silverman, Lois, primary, Abate, Francesco, primary, Steinbach, Nicole, primary, Ozturk, Sait, primary, Saal, Lao H., primary, Su, Tao, primary, Cheung, Pamela, primary, Schmidt, Hank, primary, Aaronson, Stuart, primary, Hibshoosh, Hanina, primary, Manfredi, James, primary, Rabadan, Raul, primary, and Parsons, Ramon, primary

Published
2023
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26. Figure S1 from Prediction of Lymph Node Metastasis in Breast Cancer by Gene Expression and Clinicopathological Models: Development and Validation within a Population-Based Cohort

Author

Dihge, Looket, primary, Vallon-Christersson, Johan, primary, Hegardt, Cecilia, primary, Saal, Lao H., primary, Häkkinen, Jari, primary, Larsson, Christer, primary, Ehinger, Anna, primary, Loman, Niklas, primary, Malmberg, Martin, primary, Bendahl, Pär-Ola, primary, Borg, Åke, primary, Staaf, Johan, primary, and Rydén, Lisa, primary

Published
2023
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27. Appendix S1 from Prediction of Lymph Node Metastasis in Breast Cancer by Gene Expression and Clinicopathological Models: Development and Validation within a Population-Based Cohort

Author

Dihge, Looket, primary, Vallon-Christersson, Johan, primary, Hegardt, Cecilia, primary, Saal, Lao H., primary, Häkkinen, Jari, primary, Larsson, Christer, primary, Ehinger, Anna, primary, Loman, Niklas, primary, Malmberg, Martin, primary, Bendahl, Pär-Ola, primary, Borg, Åke, primary, Staaf, Johan, primary, and Rydén, Lisa, primary

Published
2023
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29. Data from 3-Phosphoinositide–Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma

Author

Maurer, Matthew, primary, Su, Tao, primary, Saal, Lao H., primary, Koujak, Susan, primary, Hopkins, Benjamin D., primary, Barkley, Christina R., primary, Wu, Jiaping, primary, Nandula, Subhadra, primary, Dutta, Bhaskar, primary, Xie, Yuli, primary, Chin, Y. Rebecca, primary, Kim, Da-In, primary, Ferris, Jennifer S., primary, Gruvberger-Saal, Sofia K., primary, Laakso, Mervi, primary, Wang, Xiaomei, primary, Memeo, Lorenzo, primary, Rojtman, Albert, primary, Matos, Tulio, primary, Yu, Jennifer S., primary, Cordon-Cardo, Carlos, primary, Isola, Jorma, primary, Terry, Mary Beth, primary, Toker, Alex, primary, Mills, Gordon B., primary, Zhao, Jean J., primary, Murty, Vundavalli V.V.S., primary, Hibshoosh, Hanina, primary, and Parsons, Ramon, primary

Published
2023
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30. Supplementary Table 1 from The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer

Author

Jönsson, Göran, primary, Staaf, Johan, primary, Vallon-Christersson, Johan, primary, Ringnér, Markus, primary, Gruvberger-Saal, Sofia K., primary, Saal, Lao H., primary, Holm, Karolina, primary, Hegardt, Cecilia, primary, Arason, Adalgeir, primary, Fagerholm, Rainer, primary, Persson, Camilla, primary, Grabau, Dorthe, primary, Johnsson, Ellinor, primary, Lövgren, Kristina, primary, Magnusson, Linda, primary, Heikkilä, Päivi, primary, Agnarsson, Bjarni A., primary, Johannsson, Oskar T., primary, Malmström, Per, primary, Fernö, Mårten, primary, Olsson, Håkan, primary, Loman, Niklas, primary, Nevanlinna, Heli, primary, Barkardottir, Rosa B., primary, and Borg, Åke, primary

Published
2023
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31. Supplementary Information, Methods, Table 1, Figures 1-7 from 3-Phosphoinositide–Dependent Kinase 1 Potentiates Upstream Lesions on the Phosphatidylinositol 3-Kinase Pathway in Breast Carcinoma

Author

Maurer, Matthew, primary, Su, Tao, primary, Saal, Lao H., primary, Koujak, Susan, primary, Hopkins, Benjamin D., primary, Barkley, Christina R., primary, Wu, Jiaping, primary, Nandula, Subhadra, primary, Dutta, Bhaskar, primary, Xie, Yuli, primary, Chin, Y. Rebecca, primary, Kim, Da-In, primary, Ferris, Jennifer S., primary, Gruvberger-Saal, Sofia K., primary, Laakso, Mervi, primary, Wang, Xiaomei, primary, Memeo, Lorenzo, primary, Rojtman, Albert, primary, Matos, Tulio, primary, Yu, Jennifer S., primary, Cordon-Cardo, Carlos, primary, Isola, Jorma, primary, Terry, Mary Beth, primary, Toker, Alex, primary, Mills, Gordon B., primary, Zhao, Jean J., primary, Murty, Vundavalli V.V.S., primary, Hibshoosh, Hanina, primary, and Parsons, Ramon, primary

Published
2023
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32. Supplementary Figure 1 from PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma

Author

Saal, Lao H., primary, Holm, Karolina, primary, Maurer, Matthew, primary, Memeo, Lorenzo, primary, Su, Tao, primary, Wang, Xiaomei, primary, Yu, Jennifer S., primary, Malmström, Per-Olof, primary, Mansukhani, Mahesh, primary, Enoksson, Jens, primary, Hibshoosh, Hanina, primary, Borg, Åke, primary, and Parsons, Ramon, primary

Published
2023
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33. Supplementary Figure 2 from PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma

Author

Saal, Lao H., primary, Holm, Karolina, primary, Maurer, Matthew, primary, Memeo, Lorenzo, primary, Su, Tao, primary, Wang, Xiaomei, primary, Yu, Jennifer S., primary, Malmström, Per-Olof, primary, Mansukhani, Mahesh, primary, Enoksson, Jens, primary, Hibshoosh, Hanina, primary, Borg, Åke, primary, and Parsons, Ramon, primary

Published
2023
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34. Data from The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer

Author

Jönsson, Göran, primary, Staaf, Johan, primary, Vallon-Christersson, Johan, primary, Ringnér, Markus, primary, Gruvberger-Saal, Sofia K., primary, Saal, Lao H., primary, Holm, Karolina, primary, Hegardt, Cecilia, primary, Arason, Adalgeir, primary, Fagerholm, Rainer, primary, Persson, Camilla, primary, Grabau, Dorthe, primary, Johnsson, Ellinor, primary, Lövgren, Kristina, primary, Magnusson, Linda, primary, Heikkilä, Päivi, primary, Agnarsson, Bjarni A., primary, Johannsson, Oskar T., primary, Malmström, Per, primary, Fernö, Mårten, primary, Olsson, Håkan, primary, Loman, Niklas, primary, Nevanlinna, Heli, primary, Barkardottir, Rosa B., primary, and Borg, Åke, primary

Published
2023
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35. Supplementary Material from PIK3CA Mutations Correlate with Hormone Receptors, Node Metastasis, and ERBB2, and Are Mutually Exclusive with PTEN Loss in Human Breast Carcinoma

Author

Saal, Lao H., primary, Holm, Karolina, primary, Maurer, Matthew, primary, Memeo, Lorenzo, primary, Su, Tao, primary, Wang, Xiaomei, primary, Yu, Jennifer S., primary, Malmström, Per-Olof, primary, Mansukhani, Mahesh, primary, Enoksson, Jens, primary, Hibshoosh, Hanina, primary, Borg, Åke, primary, and Parsons, Ramon, primary

Published
2023
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41. Duplex Sequencing Uncovers Recurrent Low-frequency Cancer-associated Mutations in Infant and Childhood KMT2A-rearranged Acute Leukemia

Author

Pilheden, Mattias, primary, Ahlgren, Louise, additional, Hyrenius-Wittsten, Axel, additional, Gonzalez-Pena, Veronica, additional, Sturesson, Helena, additional, Hansen Marquart, Hanne Vibeke, additional, Lausen, Birgitte, additional, Castor, Anders, additional, Pronk, Cornelis Jan, additional, Barbany, Gisela, additional, Pokrovskaja Tamm, Katja, additional, Fogelstrand, Linda, additional, Lohi, Olli, additional, Norén-Nyström, Ulrika, additional, Asklin, Johanna, additional, Chen, Yilun, additional, Song, Guangchun, additional, Walsh, Michael, additional, Ma, Jing, additional, Zhang, Jinghui, additional, Saal, Lao H., additional, Gawad, Charles, additional, and Hagström-Andersson, Anna K., additional

Published
2022
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43. How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? A Study of Paired Core-Needle Biopsies and Surgical Specimens in Early Breast Cancer

Author

Saghir, Hani, primary, Veerla, Srinivas, additional, Malmberg, Martin, additional, Rydén, Lisa, additional, Ehinger, Anna, additional, Saal, Lao H., additional, Vallon-Christersson, Johan, additional, Borg, Åke, additional, Hegardt, Cecilia, additional, Larsson, Christer, additional, Haidar, Alaa, additional, Hedenfalk, Ingrid, additional, Loman, Niklas, additional, and Kimbung, Siker, additional

Published
2022
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45. Autoimmunity to selenoprotein P predicts breast cancer recurrence

Author

Demircan, Kamil, primary, Sun, Qian, additional, Bengtsson, Ylva, additional, Seemann, Petra, additional, Vallon-Christersson, Johan, additional, Malmberg, Martin, additional, Saal, Lao H., additional, Rydén, Lisa, additional, Minich, Waldemar B., additional, Borg, Åke, additional, Manjer, Jonas, additional, and Schomburg, Lutz, additional

Published
2022
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47. Duplex sequencing uncovers recurrent low-frequency cancer-associated mutations in infant and childhood KMT2A-rearranged acute leukemia

Author

Pilheden, Mattias, Ahlgren, Louise, Hyrenius-Wittsten, Axel, Gonzalez-Pena, Veronica, Sturesson, Helena, Hansen Marquart, Hanne Vibeke, Lausen, Birgitte, Castor, Anders, Pronk, Cornelis Jan, Barbany, Gisela, Pokrovskaja Tamm, Katja, Fogelstrand, Linda, Lohi, Olli, Norén-Nyström, Ulrika, Asklin, Johanna, Chen, Yilun, Song, Guangchun, Walsh, Michael, Ma, Jing, Zhang, Jinghui, Saal, Lao H., Gawad, Charles, Hagström-Andersson, Anna K., Pilheden, Mattias, Ahlgren, Louise, Hyrenius-Wittsten, Axel, Gonzalez-Pena, Veronica, Sturesson, Helena, Hansen Marquart, Hanne Vibeke, Lausen, Birgitte, Castor, Anders, Pronk, Cornelis Jan, Barbany, Gisela, Pokrovskaja Tamm, Katja, Fogelstrand, Linda, Lohi, Olli, Norén-Nyström, Ulrika, Asklin, Johanna, Chen, Yilun, Song, Guangchun, Walsh, Michael, Ma, Jing, Zhang, Jinghui, Saal, Lao H., Gawad, Charles, and Hagström-Andersson, Anna K.

Abstract

Infant acute lymphoblastic leukemia (ALL) with KMT2A-gene rearrangements (KMT2A-r) have few mutations and a poor prognosis. To uncover mutations that are below the detection of standard next-generation sequencing (NGS), a combination of targeted duplex sequencing and NGS was applied on 20 infants and 7 children with KMT2A-r ALL, 5 longitudinal and 6 paired relapse samples. Of identified nonsynonymous mutations, 87 had been previously implicated in cancer and targeted genes recurrently altered in KMT2A-r leukemia and included mutations in KRAS, NRAS, FLT3, TP53, PIK3CA, PAX5, PIK3R1, and PTPN11, with infants having fewer such mutations. Of identified cancer-associated mutations, 62% were below the resolution of standard NGS. Only 33 of 87 mutations exceeded 2% of cellular prevalence and most-targeted PI3K/RAS genes (31/33) and typically KRAS/NRAS. Five patients only had low-frequency PI3K/RAS mutations without a higher-frequency signaling mutation. Further, drug-resistant clones with FLT3D835H or NRASG13D/G12S mutations that comprised only 0.06% to 0.34% of diagnostic cells, expanded at relapse. Finally, in longitudinal samples, the relapse clone persisted as a minor subclone from diagnosis and through treatment before expanding during the last month of disease. Together, we demonstrate that infant and childhood KMT2A-r ALL harbor low-frequency cancer-associated mutations, implying a vast subclonal genetic landscape.

Published
2022
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48. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease

Author

Olsson, Eleonor, Winter, Christof, George, Anthony, Chen, Yilun, Howlin, Jillian, Tang, Man‐Hung Eric, Dahlgren, Malin, Schulz, Ralph, Grabau, Dorthe, van Westen, Danielle, Fernö, Mårten, Ingvar, Christian, Rose, Carsten, Bendahl, Pär‐Ola, Rydén, Lisa, Borg, Åke, Gruvberger‐Saal, Sofia K, Jernström, Helena, and Saal, Lao H

Published
2015
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